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      GlnR Activation Induces Peroxide Resistance in Mycobacterial Biofilms

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          Mycobacteria spontaneously form surface-associated multicellular communities, called biofilms, which display resistance to a wide range of exogenous stresses. A causal relationship between biofilm formation and emergence of stress resistance is not known. Here, we report that activation of a nitrogen starvation response regulator, GlnR, during the development of Mycobacterium smegmatis biofilms leads to peroxide resistance. The resistance arises from induction of a GlnR-dependent peroxide resistance ( gpr) gene cluster comprising of 8 ORFs (MSMEG_0565-0572). Expression of gpr increases the NADPH to NADP ratio, suggesting that a reduced cytosolic environment of nitrogen-starved cells in biofilms contributes to peroxide resistance. Increased NADPH levels from gpr activity likely support the activity of enzymes involved in nitrogen assimilation, as suggested by a higher threshold of nitrogen supplement required by a gpr mutant to form biofilms. Together, our study uniquely interlinks a nutrient sensing mechanism with emergence of stress resistance during mycobacterial biofilm development. The gpr gene cluster is conserved in several mycobacteria that can cause nosocomial infections, offering a possible explanation for their resistance to peroxide-based sterilization of medical equipment.

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          Most cited references 45

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          Computational analysis of bacterial RNA-Seq data

          Recent advances in high-throughput RNA sequencing (RNA-seq) have enabled tremendous leaps forward in our understanding of bacterial transcriptomes. However, computational methods for analysis of bacterial transcriptome data have not kept pace with the large and growing data sets generated by RNA-seq technology. Here, we present new algorithms, specific to bacterial gene structures and transcriptomes, for analysis of RNA-seq data. The algorithms are implemented in an open source software system called Rockhopper that supports various stages of bacterial RNA-seq data analysis, including aligning sequencing reads to a genome, constructing transcriptome maps, quantifying transcript abundance, testing for differential gene expression, determining operon structures and visualizing results. We demonstrate the performance of Rockhopper using 2.1 billion sequenced reads from 75 RNA-seq experiments conducted with Escherichia coli, Neisseria gonorrhoeae, Salmonella enterica, Streptococcus pyogenes and Xenorhabdus nematophila. We find that the transcriptome maps generated by our algorithms are highly accurate when compared with focused experimental data from E. coli and N. gonorrhoeae, and we validate our system’s ability to identify novel small RNAs, operons and transcription start sites. Our results suggest that Rockhopper can be used for efficient and accurate analysis of bacterial RNA-seq data, and that it can aid with elucidation of bacterial transcriptomes.
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            Oxidative stress.

            Much has been learnt about oxidative stress from studies of Escherichia coli. Key regulators of the adaptive responses in this organism are the SoxRS and OxyR transcription factors, which induce the expression of antioxidant activities in response to O2*- and H2O2 stress, respectively. Recently, a variety of biochemical assays together with the characterization of strains carrying mutations affecting the antioxidant activities and the regulators have given general insights into the sources of oxidative stress, the damage caused by oxidative stress, defenses against the oxidative stress, and the mechanisms by which the stress is perceived. These studies have also shown that the oxidative stress responses are intimately coupled to other regulatory networks in the cell.
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              Opportunistic pathogens enriched in showerhead biofilms.

              The environments we humans encounter daily are sources of exposure to diverse microbial communities, some of potential concern to human health. In this study, we used culture-independent technology to investigate the microbial composition of biofilms inside showerheads as ecological assemblages in the human indoor environment. Showers are an important interface for human interaction with microbes through inhalation of aerosols, and showerhead waters have been implicated in disease. Although opportunistic pathogens commonly are cultured from shower facilities, there is little knowledge of either their prevalence or the nature of other microorganisms that may be delivered during shower usage. To determine the composition of showerhead biofilms and waters, we analyzed rRNA gene sequences from 45 showerhead sites around the United States. We find that variable and complex, but specific, microbial assemblages occur inside showerheads. Particularly striking was the finding that sequences representative of non-tuberculous mycobacteria (NTM) and other opportunistic human pathogens are enriched to high levels in many showerhead biofilms, >100-fold above background water contents. We conclude that showerheads may present a significant potential exposure to aerosolized microbes, including documented opportunistic pathogens. The health risk associated with showerhead microbiota needs investigation in persons with compromised immune or pulmonary systems.

                Author and article information

                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                04 July 2018
                : 9
                1Division of Genetics, Wadsworth Center, New York State Department of Health , Albany, NY, United States
                2Department of Infectious Diseases and Microbiology, University of Pittsburgh , Pittsburgh, PA, United States
                3Department of Biomedical Sciences, University at Albany , Albany, NY, United States
                Author notes

                Edited by: Thomas Dick, Rutgers, The State University of New Jersey, Newark, United States

                Reviewed by: John T. Belisle, Colorado State University, United States; Tanya Parish, Infectious Disease Research Institute, United States

                *Correspondence: Anil K. Ojha, anil.ojha@

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Copyright © 2018 Yang, Richards, Gundrum and Ojha.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Figures: 7, Tables: 0, Equations: 0, References: 45, Pages: 13, Words: 0
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: RO1 AI107595
                Original Research

                Microbiology & Virology

                glnr, starvation, peroxide, biofilms, mycobacteria


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